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Open Access 01-12-2015 | Research Article

microRNA-26a suppresses recruitment of macrophages by down-regulating macrophage colony-stimulating factor expression through the PI3K/Akt pathway in hepatocellular carcinoma

Authors: Zong-Tao Chai, Xiao-Dong Zhu, Jian-Yang Ao, Wen-Quan Wang, Dong-Mei Gao, Jian Kong, Ning Zhang, Yuan-Yuan Zhang, Bo-Gen Ye, De-Ning Ma, Hao Cai, Hui-Chuan Sun

Published in: Journal of Hematology & Oncology | Issue 1/2015

Abstract

Background

microRNAs (miRNAs) have been reported to modulate macrophage colony-stimulating factor (M-CSF) and macrophages. The aim of this study was to find whether miR-26a can suppress M-CSF expression and the recruitment of macrophages.

Methods

Hepatocellular carcinoma (HCC) cell lines with decreased or increased expression of miR-26a were established in a previous study. M-CSF expression by tumor cells was measured by enzyme-linked immunosorbent assay, and cell migration assays were used to explore the effect of HCC cell lines on macrophage recruitment in vitro. Real-time PCR measured a panel of mRNAs expressed by macrophages. Xenograft models were used to observe tumor growth. Immunohistochemistry was conducted to study the relation between miR-26a expression and M-CSF expression and macrophage recruitment in patients with HCC.

Results

Ectopic expression of miR-26a reduced expression of M-CSF. The conditioned medium (CM) from HepG2 cells that overexpressed miR-26a reduced the migration ability of THP-1 cells stimulated by phorbol myristate acetate (PMA) increased expression of interleukin (IL)-12b or IL-23 mRNA and decreased expression of chemokine (C-C motif) ligand (CCL)22, CCL17, and IL-10 mRNA, in comparison to the medium from the parental HepG2 cells. These effects could be interrupted by the PI3K/Akt pathway inhibitor LY294002. Ectopic expression of miR-26a in HCC cells suppressed tumor growth, M-CSF expression, and infiltration of macrophages in tumors. Similar results were also found when using HCCLM3 cells. Furthermore, the expression of miR-26a was inversely correlated with M-CSF expression and macrophage infiltration in tumor tissues from patients with HCC.

Conclusions

miR-26a expression reduced M-CSF expression and recruitment of macrophages in HCC.

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Title: microRNA-26a suppresses recruitment of macrophages by down-regulating macrophage colony-stimulating factor expression through the PI3K/Akt pathway in hepatocellular carcinoma
Authors: Zong-Tao Chai
Xiao-Dong Zhu
Jian-Yang Ao
Wen-Quan Wang
Dong-Mei Gao
Jian Kong
Ning Zhang
Yuan-Yuan Zhang
Bo-Gen Ye
De-Ning Ma
Hao Cai
Hui-Chuan Sun
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Journal of Hematology & Oncology / Issue 1/2015
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/s13045-015-0150-4

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